The objective of this proposal is to probe events occurring in the plasma membrane (other than modification of the hormone receptor) which modulate the response of rat adipocytes to hormones. The hypothesis on which this proposal is based is that modulation of hormonal response resides within the plasma membrane where molecular events occur coupling the external surface receptor-hormone interaction with the influx of substrate or release of messenger molecules into the cytoplasm. To accomplish this, both in vivo and in vitro perturbations known to modify or which are potentially capable of modifying the response of adipocytes to hormones will be studied in regard to the following: (1) their effects on the composition of the plasma membrane of the adipocyte (e.g., lipid/protein mass ratio, lipid composition, protein composition); (2) their effects on the amount of plasma membrane per adipocyte; (3) their effects on the arrangement of the protein components in the plasma membrane of adipocytes. The perturbations to be utilized are the following: (1) acute periods of fasting; (2) refeeding following an acute fast; (3) feeding a high-fat, low-carbohydrate diet; (4) in vitro modifications of the adipocyte plasma membrane by treatment in the following ways: (a) with lipid containing vesicles of varying composition, (b) by limited exposure to proteases, phospholipases and neuraminidase. The data should yield information which can be analyzed in terms of the changes in the plasma membrane which influence the influx of substrate or the generation and release of a messenger into the cytoplasm thus resulting in the modulation of the response of adipocytes to hormones.